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Background: Nosocomial infections cause 4%–56% mortality in newborns. Several epidemiological studies have shown that transmission of opportunistic pathogens from the sink to the patient, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Serratia marcescens are associated with nosocomial infections in neonatal intensive care units (NICUs). In this project, we aimed to develop fast, accurate, and high-throughput multilocus sequence typing assays (HiMLST-Illumina) to detect opportunistic pathogens to assess their distribution in the sink environment of NICUs and their transfer to patients. Methods: Genome sequences of P. aeruginosa (n = 45), S. maltophilia (n = 23) and S. marcescens (n = 34) strains were retrieved from public genome databases to build their pangenomes, using the open-source PGAdb-builder server. The core genome was identified for each opportunistic pathogen and was searched for genes displaying the highest polymorphism. The minimal number of loci to include in a HiMLST-Illumina assay was determined by comparing topology of phylogenetic trees of concatenated loci based on genome similarity, computed as the average nucleotide identity (ANI) score. The primers used for HiMLST-Illumina schemes were designed in silico on a conserved domain and were tested on reference strains of each species. Results: Bioinformatics analyses showed that 3–4 loci (<300 base pairs per locus) distinguished strains with the same performances than ANI scores. The assays were tested using opportunistic pathogen isolates and environmental DNA originating from NICU sinks. The HiMLST-Illumina analysis of environmental DNA revealed the presence of at least 1 of the 3 studied opportunistic pathogens in 50% of sampled drains (n = 20). In a previous sampling, P. aeruginosa was isolated on selective culture media before and 48 hours after disinfection of a sink drain with chlorine. S. marcescens was also isolated from another sink 2 weeks after disinfection. Identification of the isolates was confirmed by HiMLST-Illumina analyses and will be typed to compare with clinical isolates. Conclusions: Initial in silico tests predict a high discriminating power of the HiMLST-Illumina method, suggesting that it would be possible to quickly identify strains of interest in a large number of samples. The power of this method is also in the possibility for molecular typing without a need for cultivation. Preliminary results suggest that sinks are readily colonized by opportunistic pathogens. This HiMLST-Illumina scheme will be applied in a 2-year intensive survey of NICUs in 3 hospitals in Montreal to evaluate the performance of new sink designs in limiting bioaerosol production and transmission of opportunistic pathogens to patients.
Free-living amoeba of the genus Acanthamoeba are ubiquitous protozoa involved in opportunistic and non-opportunistic infection in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Both infections have challenging characteristics such as the formation of the resistant cysts in infected tissues, hampering the treatment and most usual diagnosis depending on time-consuming and/or low sensitivity techniques. The use of monoclonal antibodies presents itself as an opportunity for the development of more effective alternative diagnostic methods, as well as an important and useful tool in the search for new therapeutic targets. This study investigated the possibility of using a previously produced monoclonal antibody (mAb3), as a diagnostic tool for the detection of Acanthamoeba trophozoites by direct and indirect flow cytometry and immunofluorescence. Immunoprecipitation assay and mass spectrometry allowed the isolation of the antibody's target and suggested it is a transporter part of the CPA (cation: proton antiporter) superfamily. In vitro tests indicate an important role of this target in Acanthamoeba's encystment physiology. Our results support the importance of studying the role of CPA2 transporters in the context of acanthamoebiasis, as this may be a way to identify new therapeutic candidates.
In this study, we aimed to capture perspectives of healthcare workers (HCWs) on coronavirus disease 2019 (COVID-19) and infection prevention and control (IPAC) measures implemented during the early phase of the COVID-19 pandemic.
A cross-sectional survey of HCWs.
HCWs from the Hospital for Sick Children, Toronto, Canada.
A self-administered survey was distributed to HCWs. We analyzed factors influencing HCW knowledge and self-reported use of personal protective equipment (PPE), concerns about contracting COVID-19 and acceptance of the recommended IPAC precautions for COVID-19.
In total, 175 HCWs completed the survey between March 6 and March 10: 35 staff physicians (20%), 24 residents or fellows (14%), 72 nurses (41%), 14 respiratory therapists (8%), 14 administration staff (8%), and 14 other employees (8%). Most of the respondents were from the emergency department (n = 58, 33%) and the intensive care unit (n = 58, 33%). Only 86 respondents (50%) identified the correct donning order; only 60 (35%) identified the correct doffing order; but the majority (n = 113, 70%) indicated the need to wash their hands immediately prior to removal of their mask and eye protection. Also, 91 (54%) respondents felt comfortable with recommendations for droplet and/or contact precautions for routine care of patients with COVID-19. HCW occupation and concerns about contracting COVID-19 outside work were associated with nonacceptance of the recommendations (P = .016 and P = .036 respectively).
As part of their pandemic response plans, healthcare institutions should have ongoing training for HCWs that focus on appropriate PPE doffing and discussions around modes of transmission of COVID-19.
This paper presents a theoretical and experimental analysis of the capabilities of the dual-input Doherty power amplifier (DPA) architecture to mitigate efficiency and output power degradations when used in a mismatched load environment. Following a simplified linear piecewise approach, an analytical demonstration is proposed to derive optimal radio frequency drives applied to the Auxiliary path of the DPA to restore power performances while avoiding large signal voltage clipping of active cells. The proposed analytical study is corroborated with harmonic balance simulated results of a C-band, 20-W GaN DPA prototype. The fabricated dual-input DPA prototype has been measured under 1.5-VSWR mismatch configurations to validate the proposed analysis.
Unlike randomized controlled trials, lack of methodological rigor is a concern about real-world evidence (RWE) studies. The objective of this study was to characterize methodological practices of studies collecting pharmacoeconomic data in a real-world setting for the management of type 2 diabetes mellitus (T2DM).
A systematic literature review was performed using the PICO framework: population consisted of T2DM patients, interventions and comparators were any intervention for T2DM care or absence of intervention, and outcomes were resource utilization, productivity loss or utility. Only RWE studies were included, defined as studies that were not clinical trials and that collected de novo data (no retrospective analysis).
The literature search identified 1,158 potentially relevant studies, among which sixty were included in the literature review. Many studies showed a lack of transparency by not mentioning the source for outcome and exposure measurement, source for patient selection, number of study sites, recruitment duration, sample size calculation, sampling method, missing data, approbation by an ethics committee, obtaining patient's consent, conflicts of interest, and funding. A significant proportion of studies had poor quality scores and was at high risk of bias.
RWE from T2DM studies lacks transparency and credibility. There is a need for good procedural practices that can increase confidence in RWE studies. Standardized methodologies specifically adapted for RWE studies collecting pharmacoeconomic data for the management of T2DM could help future reimbursement decision making in this major public health problem.
Functional capacity (FC) has been identified as a key outcome to improve real-world functioning in schizophrenia. FC is influenced by cognitive impairments, negative symptoms, self-stigma and reduced physical activity (PA). Psychosocial interventions targeting FC are still under-developed.
we conducted a quasi-experimental study evaluating the effects of an exercise-enriched integrated social cognitive remediation (SCR) intervention (RemedRugby [RR]) compared with an active control group practicing Touch Rugby (TR). To our knowledge, this is the first trial to date evaluating the effectiveness of such a program provided in a real-life environment.
Eighty-seven people with schizophrenia were included and allocated to either the RR group (n = 57) or the TR group (n = 30) according to the routine clinical practice of the recruiting center. Outcomes were evaluated at baseline and post-treatment in both groups and after 6 months of follow-up in the RR group using standardized scales for symptom severity, social functioning, self-stigma, and a large cognitive battery. After treatment we observed moderate to large improvements in social function (Personal and Social Performance Scale [PSP], p < 0.001, d = 1.255), symptom severity (Positive and Negative Syndrome Scale [PANSS] negative, p < 0.001, d = 0.827; PANSS GP, p < 0.001, d = 0.991; PANSS positive, p = 0.009, d = 0.594), verbal abstraction (p = 0.008, d = 0.554), aggression bias (p = 0.008, d = 0.627), and self-stigma (stereotype endorsement, p = 0.019, d = 0.495; discrimination experiences, p = 0.047; d = 0.389) that were specific to the RR group and were not observed in participants playing only TR. Effects were persistent over time and even larger between post-treatment and follow-up.
Exercise-enriched integrated SCR appears promising to improve real-life functioning in schizophrenia. Future research should investigate the potential effects of this intervention on neuroplasticity and physical fitness.
Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures.
The consumption of substances was investigated using biological measures (urine cotinine, cannabis, opiates, cocaine, amphetamines and barbiturates; blood carbohydrate-deficient transferrin [CDT] and gamma-glutamyl transferase [GGT]) in 486 consecutively admitted psychiatric patients, one day following their hospitalization. Patients’ self-reports of alcohol, tobacco and illicit drugs consumption were recorded. Socio-professional and familial data were also recorded.
The results show a low correlation between biological measures and self-reported consumption of alcohol and illicit drugs. Fifty-two percent of the patients under-reported their consumption of illicit drugs (kappa = .47). Patients with schizophrenia and personality disorders were more likely to disclose their illicit drug consumption relative to patients suffering from mood disorders and alcohol dependence. Fifty-six percent of patients underreported alcohol use, as evaluated by CDT (kappa = .2), and 37% underreported when using the CDT + GGT measure as an indicator. Smoking appeared to be reported adequately. In the study we observed a strong negative correlation between cannabis use and age, a strong correlation between tobacco and cannabis use, and correlations between tobacco, cannabis and alcohol consumption.
This study is the first to compare self-reports and biological measures of alcohol, tobacco and illicit drug uses in a large sample of inpatients suffering from various categories of psychiatric illnesses, allowing for cross-diagnosis comparisons.
We prove that sums of length about
of Hecke eigenvalues of automorphic forms on
do not correlate with
-periodic functions with bounded Fourier transform. This generalizes the earlier results of Munshi and Holowinsky–Nelson, corresponding to multiplicative Dirichlet characters, and applies, in particular, to trace functions of small conductor modulo primes.
This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development.
Longitudinal studies of the relationship between cognition and functioning in bipolar disorder are scarce, although cognition is thought to be a key determinant of functioning. The causal structure between cognition and psychosocial functioning in bipolar disorder is unknown.
We sought to examine the direction of causality between cognitive performance and functional outcome over 2 years in a large cohort of euthymic patients with bipolar disorder.
The sample consisted of 272 adults diagnosed with bipolar disorder who were euthymic at baseline, 12 and 24 months. All participants were recruited via the FondaMental Advanced Centers of Expertise in Bipolar Disorders. We used a battery of tests, assessing six domains of cognition at baseline and 24 months. Residual depressive symptoms and psychosocial functioning were measured at baseline and 12 and 24 months. The possible causal structure between cognition and psychosocial functioning was investigated with cross-lagged panel models with residual depressive symptoms as a covariate.
The analyses support a causal model in which cognition moderately predicts and is causally primary to functional outcome 1 year later, whereas psychosocial functioning does not predict later cognitive performance. Subthreshold depressive symptoms concurrently affected functioning at each time of measure.
Our results are compatible with an upward causal effect of cognition on functional outcome in euthymic patients with bipolar disorder. Neuropsychological assessment may help specify individual prognoses. Further studies are warranted to confirm this causal link and evaluate cognitive remediation, before or simultaneously with functional remediation, as an intervention to improve functional outcome.
We present observations on optical emission lines acquired with the scanning Fabry-Perot interferometer of the observatoire du Mont Mégantic, of the Andromeda galaxy (M31). A 765 order Fabry-Perot were used with a fast readout EM-CCD. From data obtained, kinematic maps and data points for the rotation curve of the innermost part of the galaxy are derived. Several dozen of regions have been scanned with the Fabry-Perot interferometer and narrow band interference filters. The central 10’x10’ were scanned with five different filters. Observations have been made in order to get better Hα data for kinematics purposes.
Our understanding of Saturn’s magnetosphere has been drastically changed over the last decade, since the arrival of Cassini, the first spacecraft to go into orbit around the planet. The trajectory of Cassini allowed the Saturnian magnetosphere to be studied both in the equatorial plane and at high latitudes, in a wide range of radial distances and local time sectors. This chapter reviews the current picture of Saturn’s global magnetospheric configuration and describes the local fields and particle properties in key regions like the radiation belts and the inner, middle and outer magnetosphere. The moon Enceladus, deep in the magnetosphere, is the major source of neutrals and charged particles in the magnetosphere, and in this chapter we describe how the particles are generated, transported and lost within the highly dynamic magnetosphere. We also describe how both particles and fields in the Saturnian magnetosphere vary with time, both on shorter timescales and with Saturn’s seasons. We highlight some of the most recent findings and discoveries, including a formerly unknown electric field oriented in the noon-midnight direction. Finally, we discuss magnetospheric measurements planned for the final sequence of the Cassini mission in 2017, called the “Grand Finale,” along with a list of open questions to be solved by future missions.
Senegal is experiencing a rising obesity epidemic, due to the nutrition transition occurring in most African countries, and driven by sedentary behaviour and high-calorie dietary intake. In addition, the anthropological local drivers of the social valorization of processed high-calorie food and large body sizes could expose the population to obesity risk. This study aimed to determine the impact of these biocultural factors on the nutritional status of Senegalese adults. A mixed methods approach was used, including qualitative and quantitative studies. Between 2011 and 2013, fourteen focus group discussions (n=84) and a cross-sectional quantitative survey (n=313 women; n=284 men) of adults in three different socio-ecological areas of Senegal (rural: n=204; suburban: n=206; urban: n=187) were conducted. Dietary intake (Dietary Diversity Scores), physical activity (International Physical Activity Questionnaire), body weight norms (Body Size Scale), weight and health statuses (anthropometric measures and blood pressure) were measured. Middle-aged and older Senegalese women were found to value overweight/obesity more than younger Senegalese in all regions. In addition, young urban/suburban adults had a tendency for daily snacking whilst urban/suburban adults tended to be less physically active and had higher anthropometric means. A binary logistic regression model showed that being female, older, living in urban/suburban areas and valuing larger body size were independently associated with being overweight/obese, but not high-calorie diet. Univariate analyses showed that lower physical activity and higher socioeconomic status were associated with being overweight/obese. Finally, overweight/obesity, which is low in men, is associated with hypertension in the total sample. The nutrition transition is currently underway in Senegal’s urban/suburban areas, with older women being more affected. Since several specific biocultural factors jointly contribute to this phenomenon, the study’s findings suggest the need for local public health interventions that target women and which account for the anthropological specificities of the Senegalese population.
Automated storage and retrieval systems are principal components of modern production and warehouse facilities. In particular, automated guided vehicles nowadays substitute human-operated pallet trucks in transporting production materials between storage locations and assembly stations. While low-level control systems take care of navigating such driverless vehicles along programmed routes and avoid collisions even under unforeseen circumstances, in the common case of multiple vehicles sharing the same operation area, the problem remains how to set up routes such that a collection of transport tasks is accomplished most effectively. We address this prevalent problem in the context of car assembly at Mercedes-Benz Ludwigsfelde GmbH, a large-scale producer of commercial vehicles, where routes for automated guided vehicles used in the production process have traditionally been hand-coded by human engineers. Such ad-hoc methods may suffice as long as a running production process remains in place, while any change in the factory layout or production targets necessitates tedious manual reconfiguration, not to mention the missing portability between different production plants. Unlike this, we propose a declarative approach based on Answer Set Programming to optimize the routes taken by automated guided vehicles for accomplishing transport tasks. The advantages include a transparent and executable problem formalization, provable optimality of routes relative to objective criteria, as well as elaboration tolerance towards particular factory layouts and production targets. Moreover, we demonstrate that our approach is efficient enough to deal with the transport tasks evolving in realistic production processes at the car factory of Mercedes-Benz Ludwigsfelde GmbH.
Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach.
We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD.
One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit.
This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been recently described as an innovative and effective tool for identifying arthropods and mosquito blood meal sources. To test this approach in the context of an entomological survey in the field, mosquitoes were collected from five ecologically distinct areas of Mali. We successfully analysed the blood meals from 651 mosquito abdomens crushed on Whatman filter paper (WFPs) in the field using MALDI-TOF MS. The legs of 826 mosquitoes were then submitted for MALDI-TOF MS analysis in order to identify the different mosquito species. Eight mosquito species were identified, including Anopheles gambiae Giles, Anopheles coluzzii, Anopheles arabiensis, Culex quinquefasciatus, Culex neavei, Culex perexiguus, Aedes aegypti and Aedes fowleri in Mali. The field mosquitoes for which MALDI-TOF MS did not provide successful identification were not previously available in our database. These specimens were subsequently molecularly identified. The WFP blood meal sources found in this study were matched against human blood (n = 619), chicken blood (n = 9), cow blood (n = 9), donkey blood (n = 6), dog blood (n = 5) and sheep blood (n = 3). This study reinforces the fact that MALDI-TOF MS is a promising tool for entomological surveys.
To assess under real community settings the effectiveness of the WHO strategy of home fortification of foods (HFF) with multiple-micronutrient powders on Hb change, anaemia and weight in children.
A pragmatic cluster-randomized controlled trial.
Forty villages in the Nioro Circle in Mali and 722 children aged 6–23 months were randomized to the intervention or control group. The intervention consisted of a daily dose of multiple-micronutrient powder for 3 months; in the control group, no supplement was given. In both groups, mothers received group education on child complementary feeding. Changes in weight, Hb concentration and anaemia were assessed as primary outcomes at baseline and 3 months. The HFF effect was determined using regression analyses and quantile regression with standard errors taking account of the cluster design.
Children aged 6–23 months.
Overall prevalence of anaemia in the sample was high: 90 %. HFF provided a modest but statistically significant Hb change v. no intervention (0·50 v. 0·09 g/dl, P=0·023). Prevalence of anaemia changed little: 91·3–85·8 % (P=0·04) in the intervention group v. 88·1–87·5 % % (P=0·86) in the control group. Proportion of severe anaemia was reduced by 84 % (from 9·8 to 1·6 %) in the intervention group, but increased in the control group (from 8·5 to 10·8 %). No effect was observed on weight.
The WHO HFF strategy to fight anaemia showed a modest change on Hb concentration and significantly reduced the rate of severe anaemia.
We assessed clinicians’ continuing professional development (CPD) needs at family practice teaching clinics in the province of Quebec. Our mixed methodology design comprised an environmental scan of training programs at four family medicine departments, an expert panel to determine priority clinical situations for senior care, a supervisors survey to assess their perceived CPD needs, and interviews to help understand the rationale behind their needs. From the environmental scan, the expert panel selected 13 priority situations. Key needs expressed by the 352 survey respondents (36% response rate) included behavioral and psychological symptoms of dementia, polypharmacy, depression, and cognitive disorders. Supervisors explained that these situations were sometimes complex to diagnose and manage because of psychosocial aspects, challenges of communicating with patients and families, and coordination of interprofessional teams. Supervisors also reported more CPD needs in long-term and home care, given the presence of caregivers and complexity of senior care in these settings.
Decision-making about replacement or modification of an implantable cardioverter defibrillator (ICD) must be patient-centered and clinically appropriate. We engaged both patients and health care professionals in a multi-method approach in order to recommend structures and processes that facilitate informed and shared decision-making.
A systematic literature review (2000 to 2017) was performed focusing on the patient's perspective and the optimal organization of structures and processes for decision-making. A province-wide field evaluation based on medical chart review was carried out to provide ‘real world’ evidence in Québec's six ICD implanting centers (1 July to 31 December, 2016; N = 418). Patients and health care professionals reviewed the findings of the review and field evaluation, and deliberated recommendations in an anonymous manner by electronic mail. A joint meeting focused on proposed recommendations concerning shared decision-making.
The patients provided feedback on the literature review based on their ICD experience, and highlighted the need for better and more interactive decision aids, clinical information and time, and a private space for sensitive discussions. The field evaluation underlined the variability of treatment choices at the time of replacement and that more than one in ten patients had undergone ICD deactivation. Proposed recommendations focus on multi-disciplinary, integrated follow-up of patients and outline best practice for incorporating patient wishes and life objectives when discussing treatment options. The multi-round consultation process allowed both patients and professionals to co-construct recommendations with our evaluation team.
This multi-method approach enriched our interpretation of literature and ‘real world’ data and facilitated identification and prioritization of important themes. Partnership with both patients and clinicians added a new and energizing dynamic to our evaluation and recommendation processes. We acknowledge the contribution of the members of the patient committee and the clinical experts committee.